Siloxane prepolymer containing pendant and end-capping cationic and polymerizable groups

ABSTRACT

The present invention relates to polymeric compositions useful in the manufacture of biocompatible medical devices. More particularly, the present invention relates to certain cationic random copolymers capable of polymerization to form polymeric compositions having desirable physical characteristics useful in the manufacture of ophthalmic devices. Such properties include the ability to extract the polymerized medical devices with water. This avoids the use of organic solvents as is typical in the art. The polymer compositions comprise siloxane prepolymer containing pendant and end-capping cationic and polymerizable groups.

PRIORITY CLAIMS TO PRIOR APPLICATIONS

This application claims the benefit of Provisional Patent ApplicationNo. 60/756,982 filed Jan. 9, 2006 and is incorporated herein byreference

FIELD

The present invention relates to polymeric compositions useful in themanufacture of biocompatible medical devices. More particularly, thepresent invention relates to certain cationic random copolymers capableof polymerization to form polymeric compositions having desirablephysical characteristics useful in the manufacture of ophthalmicdevices. Such properties include the ability to extract the polymerizedmedical devices with water. This avoids the use of organic solvents asis typical in the art. The polymer compositions comprise polymerizedsiloxane prepolymer containing pendant and end-capping cationic andpolymerizable groups.

BACKGROUND AND SUMMARY

Various articles, including biomedical devices, are formed oforganosilicon-containing materials. One class of organosilicon materialsuseful for biomedical devices, such as soft contact lenses, issilicon-containing hydrogel materials. A hydrogel is a hydrated,crosslinked polymeric system that contains water in an equilibriumstate. Hydrogel contact lenses offer relatively high oxygen permeabilityas well as desirable biocompatibility and comfort. The inclusion of asilicon-containing material in the hydrogel formulation generallyprovides higher oxygen permeability since silicon based materials havehigher oxygen permeability than water.

Another class of organosilicon materials is rigid, gas permeablematerials used for hard contact lenses. Such materials are generallyformed of silicon or fluorosilicon copolymers. These materials areoxygen permeable, and more rigid than the materials used for softcontact lenses. Organosilicon-containing materials useful for biomedicaldevices, including contact lenses, are disclosed in the following U.S.patents: U.S. Pat. No. 4,686,267 (Ellis et al.); U.S. Pat. No. 5,034,461(Lai et al.); and U.S. Pat. No. 5,070,215 (Bambury et al.).

In addition, traditional siloxane-type monomers are hydrophobic andlenses made with them frequently require additional treatment to providea hydrophilic surface. Although not wishing to be bound by a particulartheory, the inventors believe that providing a charged siloxane-typerandom copolymer such as the quaternary siloxane-type random copolymersdisclosed herein results in a hydrophilic siloxane-type randomcopolymer. It is believed that the hydrophilic quaternary groupsinteract with the electronegative portion of the polar water molecule.

Soft contact lens materials are made by polymerizing and crosslinkinghydrophilic monomers such as 2-hydroxyethylmethyacrylate,N-vinyl-2-pyrrolidone, and combinations thereof. The polymers producedby polymerizing these hydrophilic monomers exhibit significanthydrophilic character themselves and are capable of absorbing asignificant amount of water in their polymeric matrices. Due to theirability to absorb water, these polymers are often referred to as“hydrogels”. These hydrogels are optically clear and, due to their highlevels of water of hydration, are particularly useful materials formaking soft contact lenses. Siloxane-type monomers are well known to bepoorly soluble in water as well as hydrophilic solvents and monomers andare therefore difficult to copolymerize and process using standardhydrogel techniques. Therefore, there is a need for new siloxane-typerandom copolymers that have improved solubility in the materials,specifically the diluents, used to make hydrogel lenses. Further thereis a need for random copolymers that result in a polymerized medicaldevice that is extractable in water instead of the organic solvents usedin the prior art.

The present invention provides novel cationic organosilicon-containingrandom copolymers which are useful in articles such as biomedicaldevices including contact lenses.

BRIEF DESCRIPTION OF THE DRAWINGS

None

DETAILED DESCRIPTION

In a first aspect, the invention relates to random copolymers of formula(I):

wherein R1 and R5 are the same or different and are selected from one ofthe following formulae:

with the proviso that when R5 is the same and is formula II, R1 is notof formula I, x is 0 to 1000, y is 1 to 300, L can be the same ordifferent and is selected from the group consisting of urethanes,carbonates, carbamates, carboxyl ureidos, sulfonyls, a straight orbranched C1-C30 alkyl group, a C1-C30 fluoroalkyl group, a C1-C20 estergroup, an alkyl ether, cycloalkyl ether, cycloalkenyl ether, aryl ether,arylalkyl ether, a polyether containing group, an ureido group, an amidegroup, an amine group, a substituted or unsubstituted C1-C30 alkoxygroup, a substituted or unsubstituted C3-C30 cycloalkyl group, asubstituted or unsubstituted C3-C30 cycloalkenyl group, a substituted orunsubstituted C5-C30 aryl group, a substituted or unsubstituted C5-C30arylalkyl group, a substituted or unsubstituted C5-C30 heteroaryl group,a substituted or unsubstituted C3-C30 heterocyclic ring, a substitutedor unsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, a C5-C30 fluoroaryl group,or a hydroxyl substituted alkyl ether and combinations thereof.

X⁻ is at least a single charged counter ion. Examples of single chargecounter ions include the group consisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻,CH₃CO₂ ⁻, HCO₃ ⁻, CH₃SO₄ ⁻, p-toluenesulfonate, HSO₄ ⁻, H₂PO₄ ⁻, NO₃ ⁻,and CH₃CH(OH)CO₂ ⁻. Examples of dual charged counter ions would includeSO₄ ²⁻, CO₃ ²⁻ and HPO₄ ²⁻. Other charged counter ions would be obviousto one of ordinary skill in the art. It should be understood that aresidual amount of counter ion may be present in the hydrated product.Therefore, the use of toxic counterions is to be discouraged. Likewise,it should be understood that, for a singularly charged counterion, theratio of counterion and quaternary siloxanyl will be 1:1. Counterions ofgreater negative charge will result in differing ratios based upon thetotal charge of the counterion.

R2 and R3 are independently hydrogen, a straight or branched C1-C30alkyl group, a C1-C30 fluoroalkyl group, a C1-C20 ester group, an alkylether, cycloalkyl ether, ether, cycloalkenyl ether, aryl ether,arylalkyl ether, a polyether containing group, an ureido group, an amidegroup, an amine group, a substituted or unsubstituted C1-C30 alkoxygroup, a substituted or unsubstituted C3-C30 cycloalkylalkyl group, asubstituted or unsubstituted C3-C30 cycloalkenyl group, a substituted orunsubstituted C5-C30 aryl group, a substituted or unsubstituted C5-C30arylalkyl group, a substituted or unsubstituted C5-C30 heteroaryl group,a substituted or unsubstituted C3-C30 heterocyclic ring, a substitutedor unsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, fluorine, a C5-C30fluoroaryl group, or a hydroxyl group. R4 is hydrogen or methyl.

Representative examples of urethanes for use herein include, by way ofexample, a secondary amine linked to a carboxyl group which may also belinked to a further group such as an alkyl. Likewise the secondary aminemay also be linked to a further group such as an alkyl.

Representative examples of carbonates for use herein include, by way ofexample, alkyl carbonates, aryl carbonates, and the like.

Representative examples of carbamates, for use herein include, by way ofexample, alkyl carbamates, aryl carbamates, and the like.

Representative examples of carboxyl ureidos, for use herein include, byway of example, alkyl carboxyl ureidos, aryl carboxyl ureidos, and thelike.

Representative examples of sulfonyls for use herein include, by way ofexample, alkyl sulfonyls, aryl sulfonyls, and the like.

Representative examples of alkyl groups for use herein include, by wayof example, a straight or branched hydrocarbon chain radical containingcarbon and hydrogen atoms of from 1 to about 18 carbon atoms with orwithout unsaturation, to the rest of the molecule, e.g., methyl, ethyl,n-propyl, 1-methylethyl (isopropyl), n-butyl, n-pentyl, etc., and thelike.

Representative examples of fluoroalkyl groups for use herein include, byway of example, a straight or branched alkyl group as defined abovehaving one or more fluorine atoms attached to the carbon atom, e.g.,—CF3, —CF2CF3, —CH2CF3, —CH2CF2H, —CF2H and the like.

Representative examples of ester groups for use herein include, by wayof example, a carboxylic acid ester having one to 20 carbon atoms andthe like.

Representative examples of ether or polyether containing groups for useherein include, by way of example, an alkyl ether, cycloalkyl ether,cycloalkylalkyl ether, cycloalkenyl ether, aryl ether, arylalkyl etherwherein the alkyl, cycloalkyl, cycloalkenyl, aryl, and arylalkyl groupsare defined above, e.g., alkylene oxides, poly(alkylene oxide)s such asethylene oxide, propylene oxide, butylene oxide, poly(ethylene oxide)s,poly(ethylene glycol)s, poly(propylene oxide)s, poly(butylene oxide)sand mixtures or copolymers thereof, an ether or polyether group of thegeneral formula —R8OR9, wherein R8 is a bond, an alkyl, cycloalkyl oraryl group as defined above and R9 is an alkyl, cycloalkyl or aryl groupas defined above, e.g., —CH2CH2OC6H5 and —CH2CH2OC2H5, and the like.

Representative examples of amide groups for use herein include, by wayof example, an amide of the general formula —R10C(O)NR11R12 wherein R10,R11 and R12 are independently C1-C30 hydrocarbons, e.g., R10 can bealkylene groups, arylene groups, cycloalkylene groups and R11 and R12can be alkyl groups, aryl groups, and cycloalkyl groups as definedherein and the like.

Representative examples of amine groups for use herein include, by wayof example, an amine of the general formula —R13N R14R15 wherein R13 isa C2-C30 alkylene, arylene, or cycloalkylene and R14 and R15 areindependently C1-C30 hydrocarbons such as, for example, alkyl groups,aryl groups, or cycloalkyl groups as defined herein, and the like.

Representative examples of an ureido group for use herein include, byway of example, an ureido group having one or more substituents orunsubstituted ureido. The ureido group preferably is an ureido grouphaving 1 to 12 carbon atoms. Examples of the substituents include alkylgroups and aryl groups. Examples of the ureido group include3-methylureido, 3,3-dimethylureido, and 3-phenylureido.

Representative examples of alkoxy groups for use herein include, by wayof example, an alkyl group as defined above attached via oxygen linkageto the rest of the molecule, i.e., of the general formula -OR20, whereinR20 is an alkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl or anarylalkyl as defined above, e.g., —OCH3, —OC2H5, or —OC6H5, and thelike.

Representative examples of cycloalkyl groups for use herein include, byway of example, a substituted or unsubstituted non-aromatic mono ormulticyclic ring system of about 3 to about 18 carbon atoms such as, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,perhydronapththyl, adamantyl and norbornyl groups bridged cyclic groupor spirobicyclic groups, e.g., sprio-(4,4)-non-2-yl and the like,optionally containing one or more heteroatoms, e.g., O and N, and thelike.

Representative examples of cycloalkenyl groups for use herein include,by way of example, a substituted or unsubstituted cyclic ring-containingradical containing from about 3 to about 18 carbon atoms with at leastone carbon-carbon double bond such as, for example, cyclopropenyl,cyclobutenyl, cyclopentenyl and the like, wherein the cyclic ring canoptionally contain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of aryl groups for use herein include, by way ofexample, a substituted or unsubstituted monoaromatic or polyaromaticradical containing from about 5 to about 25 carbon atoms such as, forexample, phenyl, naphthyl, tetrahydronapthyl, indenyl, biphenyl and thelike, optionally containing one or more heteroatoms, e.g., O and N, andthe like.

Representative examples of arylalkyl groups for use herein include, byway of example, a substituted or unsubstituted aryl group as definedabove directly bonded to an alkyl group as defined above, e.g.,—CH2C6H5, —C2H5C6H5 and the like, wherein the aryl group can optionallycontain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of fluoroaryl groups for use herein include, byway of example, an aryl group as defined above having one or morefluorine atoms attached to the aryl group.

Representative examples of heterocyclic ring groups for use hereininclude, by way of example, a substituted or unsubstituted stable 3 toabout 15 membered ring radical, containing carbon atoms and from one tofive heteroatoms, e.g., nitrogen, phosphorus, oxygen, sulfur andmixtures thereof. Suitable heterocyclic ring radicals for use herein maybe a monocyclic, bicyclic or tricyclic ring system, which may includefused, bridged or spiro ring systems, and the nitrogen, phosphorus,carbon, oxygen or sulfur atoms in the heterocyclic ring radical may beoptionally oxidized to various oxidation states. In addition, thenitrogen atom may be optionally quaternized; and the ring radical may bepartially or fully saturated (i.e., heteroaromatic or heteroarylaromatic). Examples of such heterocyclic ring radicals include, but arenot limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl,benzofurnyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl,naphthyridinyl, perhydroazepinyl, phenazinyl, phenothiazinyl,phenoxazinyl, phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl,quinoxalinyl, quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl,tetrahydroisouinolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl,2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl,4-piperidonyl, pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl,oxazolyl, oxazolinyl, oxasolidinyl, triazolyl, indanyl, isoxazolyl,isoxasolidinyl, morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl,isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl,indolinyl, isoindolinyl, octahydroindolyl, octahydroisoindolyl,quinolyl, isoquinolyl, decahydroisoquinolyl, benzimidazolyl,thiadiazolyl, benzopyranyl, benzothiazolyl, benzooxazolyl, furyl,tetrahydrofurtyl, tetrahydropyranyl, thienyl, benzothienyl,thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone,dioxaphospholanyl, oxadiazolyl, chromanyl, isochromanyl and the like andmixtures thereof.

Representative examples of heteroaryl groups for use herein include, byway of example, a substituted or unsubstituted heterocyclic ring radicalas defined above. The heteroaryl ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heteroarylalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heteroarylring radical as defined above directly bonded to an alkyl group asdefined above. The heteroarylalkyl radical may be attached to the mainstructure at any carbon atom from the alkyl group that results in thecreation of a stable structure.

Representative examples of heterocyclo groups for use herein include, byway of example, a substituted or unsubstituted heterocylic ring radicalas defined above. The heterocyclo ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heterocycloalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heterocylicring radical as defined above directly bonded to an alkyl group asdefined above. The heterocycloalkyl radical may be attached to the mainstructure at carbon atom in the alkyl group that results in the creationof a stable structure.

Representative examples of a “polymerizable ethylenically unsaturatedorganic radicals” include, by way of example, (meth)acrylate-containingradicals, (meth)acrylamide-containing radicals,vinylcarbonate-containing radicals, vinylcarbamate-containing radicals,styrene-containing radicals and the like. In one embodiment, apolymerizable ethylenically unsaturated organic radical can berepresented by the general formula:

wherein R21 is hydrogen, fluorine or methyl; R22 is independentlyhydrogen, fluorine, an alkyl radical having 1 to 6 carbon atoms, or a—CO—Y—R24 radical wherein Y is —O—, —S— or —NH— and R24 is a divalentalkylene radical having 1 to about 10 carbon atoms.

The substituents in the ‘substituted alkyl’, ‘substituted alkoxy’,‘substituted cycloalkyl’, ‘substituted cycloalkenyl’, ‘substitutedarylalkyl’, ‘substituted aryl’, ‘substituted heterocyclic ring’,‘substituted heteroaryl ring,’‘substituted heteroarylalkyl’,‘substituted heterocycloalkyl ring’, ‘substituted cyclic ring’ and‘substituted carboxylic acid derivative’ may be the same or differentand include one or more substituents such as hydrogen, hydroxy, halogen,carboxyl, cyano, nitro, oxo (αO), thio(═S), substituted or unsubstitutedalkyl, substituted or unsubstituted alkoxy, substituted or unsubstitutedalkenyl, substituted or unsubstituted alkynyl, substituted orunsubstituted aryl, substituted or unsubstituted arylalkyl, substitutedor unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl,substituted or unsubstituted amino, substituted or unsubstituted aryl,substituted or unsubstituted heteroaryl, substituted heterocycloalkylring, substituted or unsubstituted heteroarylalkyl, substituted orunsubstituted heterocyclic ring, substituted or unsubstituted guanidine,—COORx, —C(O)Rx, —C(S)Rx, —C(O)NRxRy, —C(O)ONRxRy, —NRxCONRyRz,—N(Rx)SORy, —N(Rx)SO2Ry, —(═N—N(Rx)Ry), —NRxC(O)ORy, —NRxRy,—NRxC(O)Ry—, —NRxC(S)Ry —NRxC(S)NRyRz, —SONRxRy—, —SO2NRxRy—, —ORx,—ORxC(O)NRyRz, ‘3ORxC(O)ORy—, —OC(O)Rx, —OC(O)NRxRy, —RxNRyC(O)Rz,—RxORy, —RxC(O)ORy, —RxC(O)NRyRz, —RxC(O)Rx, —RxOC(O)Ry, —SRx, —SORx,—SO2Rx, —ONO2, wherein Rx, Ry and Rz in each of the above groups can bethe same or different and can be a hydrogen atom, substituted orunsubstituted alkyl, substituted or unsubstituted alkoxy, substituted orunsubstituted alkenyl, substituted or unsubstituted alkynyl, substitutedor unsubstituted aryl, substituted or unsubstituted arylalkyl,substituted or unsubstituted cycloalkyl, substituted or unsubstitutedcycloalkenyl, substituted or unsubstituted amino, substituted orunsubstituted aryl, substituted or unsubstituted heteroaryl, substitutedheterocycloalkyl ring, substituted or unsubstituted heteroarylalkyl, ora substituted or unsubstituted heterocyclic ring.

A schematic representation of synthetic methods for making the novelcationic silicon-containing random copolymers disclosed herein isprovided below:

In a second aspect, the invention includes articles formed of deviceforming monomer mixes comprising the monomers of formulas (I)-(V).According to preferred embodiments, the article is the polymerizationproduct of a mixture comprising the aforementioned monomers and at leasta second monomer. The invention is applicable to a wide variety ofpolymeric materials, either rigid or soft. Especially preferredpolymeric materials are lenses including contact lenses, phakic andaphakic intraocular lenses and corneal implants although all polymericmaterials including biomaterials are contemplated as being within thescope of this invention. Preferred articles are optically clear anduseful as a contact lens.

The present invention also provides medical devices such as heart valvesand films, surgical devices, vessel substitutes, intrauterine devices,membranes, diaphragms, surgical implants, blood vessels, artificialureters, artificial breast tissue and membranes intended to come intocontact with body fluid outside of the body, e.g., membranes for kidneydialysis and heart/lung machines and the like, catheters, mouth guards,denture liners, ophthalmic devices, and especially contact lenses.

Silicon containing hydrogels are prepared by polymerizing a mixturecontaining at least one silicon-containing monomer and at least onehydrophilic monomer. The silicon-containing monomer may function as acrosslinking agent (a crosslinker being defined as a monomer havingmultiple polymerizable functionalities) or a separate crosslinker may beemployed.

An early example of a silicon-containing contact lens material isdisclosed in U.S. Pat. No. 4,153,641 (Deichert et al assigned to Bausch& Lomb Incorporated). Lenses are made from poly(organosiloxane) monomerswhich are α, ω terminally bonded through a divalent hydrocarbon group toa polymerized activated unsaturated group. Various hydrophobicsilicon-containing prepolymers such as1,3-bis(methacryloxyalkyl)-polysiloxanes were copolymerized with knownhydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA).

U.S. Pat. No. 5,358,995 (Lai et al) describes a silicon containinghydrogel which is comprised of an acrylic ester-capped polysiloxaneprepolymer, polymerized with a bulky polysiloxanylalkyl (meth)acrylatemonomer, and at least one hydrophilic monomer. Lai et al is assigned toBausch & Lomb Incorporated and the entire disclosure is incorporatedherein by reference. The acrylic ester-capped polysiloxane prepolymer,commonly known as M₂ D_(x) consists of two acrylic ester end groups and“x” number of repeating dimethylsiloxane units. The preferred bulkypolysiloxanylalkyl (meth)acrylate monomers are TRIS-type(methacryloxypropyl tris(trimethylsiloxy)silane) with the hydrophilicmonomers being either acrylic- or vinyl-containing.

Other examples of silicon-containing monomer mixtures which may be usedwith this invention include the following: vinyl carbonate and vinylcarbamate monomer mixtures as disclosed in U.S. Pat. Nos. 5,070,215 and5,610,252 (Bambury et al); fluorosilicon monomer mixtures as disclosedin U.S. Pat. Nos. 5,321,108; 5,387,662 and 5,539,016 (Kunzler et al);fumarate monomer mixtures as disclosed in U.S. Pat. Nos. 5,374,662;5,420,324 and 5,496,871 (Lai et al) and urethane monomer mixtures asdisclosed in U.S. Pat. Nos. 5,451,651; 5,648,515; 5,639,908 and5,594,085(Lai et al), all of which are commonly assigned to assigneeherein Bausch & Lomb Incorporated, and the entire disclosures of whichare incorporated herein by reference.

Examples of non-silicon hydrophobic materials include alkyl acrylatesand methacrylates.

The cationic silicon-containing monomers may be copolymerized with awide variety of hydrophilic monomers to produce silicon hydrogel lenses.Suitable hydrophilic monomers include: unsaturated carboxylic acids,such as methacrylic and acrylic acids; acrylic substituted alcohols,such as 2-hydroxyethyl methacrylate and 2-hydroxyethyl acrylate; vinyllactams, such as N-vinylpyrrolidone (NVP) and 1-vinylazonan-2-one; andacrylamides, such as methacrylamide and N,N-dimethylacrylamide (DMA).

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. Nos. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Hydrophobic cross-linkers would include methacrylates such as ethyleneglycol dimethacrylate (EGDMA) and allyl methacrylate (AMA). In contrastto traditional silicon hydrogel monomer mixtures, the monomer mixturescontaining the quaternized silicon random copolymer of the inventionherein are relatively water soluble as compared to prior art siliconcontaining hydrogel forming monomers. This feature provides advantagesover traditional silicon hydrogel monomer mixtures in that there is lessrisk of incompatibility phase separation resulting in hazy lenses, thepolymerized materials are extractable with water. However, when desiredtraditional organic extraction methods may also be used. In addition,the extracted lenses demonstrate a good combination of oxygenpermeability (Dk) and low modulus, properties known to be important toobtaining desirable contact lenses. Moreover, lenses prepared with thequaternized silicon random copolymers of the invention herein arewettable even without surface treatment, provide dry mold release, donot require solvents in the monomer mix (although solvents such asglycerol may be used) the extracted polymerized material is notcytotoxic and the surface is lubricious to the touch. In cases where thepolymerized monomer mix containing the quaternized silicon randomcopolymers of the invention herein do not demonstrate a desirable tearstrength, toughening agents such as TBE (4-t-butyl-2-hydroxycyclohexylmethacrylate) may be added to the monomer mix. Other toughening agentsare well known to those of ordinary skill in the art and may also beused when needed.

Although an advantage of the cationic silicon-containing randomcopolymers disclosed herein is that they are relatively water solubleand also soluble in their comonomers, an organic diluent may be includedin the initial monomeric mixture. As used herein, the term “organicdiluent” encompasses organic compounds which minimize incompatibility ofthe components in the initial monomeric mixture and are substantiallynonreactive with the components in the initial mixture. Additionally,the organic diluent serves to minimize phase separation of polymerizedproducts produced by polymerization of the monomeric mixture. Also, theorganic diluent will generally be relatively non-inflammable.

Contemplated organic diluents include tert-butanol (TBA); diols, such asethylene glycol and polyols, such as glycerol. Preferably, the organicdiluent is sufficiently soluble in the extraction solvent to facilitateits removal from a cured article during the extraction step. Othersuitable organic diluents would be apparent to a person of ordinaryskill in the art.

The organic diluent is included in an amount effective to provide thedesired effect. Generally, the diluent is included at 5 to 60% by weightof the monomeric mixture, with 10 to 50% by weight being especiallypreferred.

According to the present process, the monomeric mixture, comprising atleast one hydrophilic monomer, at least one cationic silicon-containingrandom copolymer as described herein and optionally the organic diluent,is shaped and cured by conventional methods such as static casting orspincasting.

Lens formation can be by free radical polymerization such asazobisisobutyronitrile (AIBN) and peroxide catalysts using initiatorsand under conditions such as those set forth in U.S. Pat. No. 3,808,179,incorporated herein by reference. Photo initiation of polymerization ofthe monomer mixture as is well known in the art may also be used in theprocess of forming an article as disclosed herein. Colorants and thelike may be added prior to monomer polymerization.

Subsequently, a sufficient amount of unreacted monomer and, whenpresent, organic diluent is removed from the cured article to improvethe biocompatibility of the article. Release of non-polymerized monomersinto the eye upon installation of a lens can cause irritation and otherproblems. Unlike other monomer mixtures that must be extracted withflammable solvents such as isopropyl alcohol, because of the propertiesof the novel quaternized siloxane random copolymers disclosed herein,non-flammable solvents may be used for the extraction process.

Once the biomaterials formed from the polymerized monomer mix containingthe cationic silicon containing random copolymers disclosed herein areformed they are then extracted to prepare them for packaging andeventual use. Extraction is accomplished by exposing the polymerizedmaterials to various solvents such as water, tert-butanol, etc. forvarying periods of time. For example, one extraction process is toimmerse the polymerized materials in water for about three minutes,remove the water and then immerse the polymerized materials in anotheraliquot of water for about three minutes, remove that aliquot of waterand then autoclave the polymerized material in water or buffer solution.

Following extraction of unreacted monomers and any organic diluent, theshaped article, for example an RGP lens, is optionally machined byvarious processes known in the art. The machining step includes lathecutting a lens surface, lathe cutting a lens edge, buffing a lens edgeor polishing a lens edge or surface. The present process is particularlyadvantageous for processes wherein a lens surface is lathe cut, sincemachining of a lens surface is especially difficult when the surface istacky or rubbery.

Generally, such machining processes are performed before the article isreleased from a mold part. After the machining operation, the lens canbe released from the mold part and hydrated. Alternately, the articlecan be machined after removal from the mold part and then hydrated.

Mechanical properties and Oxygen Permeability. Modulus and elongationtests were conducted according to ASTM D-1708a, employing an Instron(Model 4502) instrument where the hydrogel film sample is immersed inborate buffered saline; an appropriate size of the film sample is gaugelength 22 mm and width 4.75 mm, where the sample further has endsforming a dog bone shape to accommodate gripping of the sample withclamps of the Instron instrument, and a thickness of 200+50 microns.

Oxygen permeability (also referred to as Dk) was determined by thefollowing procedure. Other methods and/or instruments may be used aslong as the oxygen permeability values obtained therefrom are equivalentto the described method. The oxygen permeability of silicone hydrogelsis measured by the polarographic method (ANSI Z80.20-1998) using an O2Permeometer Model 201T instrument (Createch, Albany, Calif. USA) havinga probe containing a central, circular gold cathode at its end and asilver anode insulated from the cathode. Measurements are taken only onpre-inspected pinhole-free, flat silicone hydrogel film samples of threedifferent center thicknesses ranging from 150 to 600 microns. Centerthickness measurements of the film samples may be measured using aRehder ET-1 electronic thickness gauge. Generally, the film samples havethe shape of a circular disk. Measurements are taken with the filmsample and probe immersed in a bath containing circulating phosphatebuffered saline (PBS) equilibrated at 35° C.±0.2°. Prior to immersingthe probe and film sample in the PBS bath, the film sample is placed andcentered on the cathode premoistened with the equilibrated PBS, ensuringno air bubbles or excess PBS exists between the cathode and the filmsample, and the film sample is then secured to the probe with a mountingcap, with the cathode portion of the probe contacting only the filmsample. For silicone hydrogel films, it is frequently useful to employ aTeflon polymer membrane, e.g., having a circular disk shape, between theprobe cathode and the film sample. In such cases, the Teflon membrane isfirst placed on the pre-moistened cathode, and then the film sample isplaced on the Teflon membrane, ensuring no air bubbles or excess PBSexists beneath the Teflon membrane or film sample. Once measurements arecollected, only data with correlation coefficient value (R2) of 0.97 orhigher should be entered into the calculation of Dk value. At least twoDk measurements per thickness, and meeting R2 value, are obtained. Usingknown regression analyses, oxygen permeability (Dk) is calculated fromthe film samples having at least three different thicknesses. Any filmsamples hydrated with solutions other than PBS are first soaked inpurified water and allowed to equilibrate for at least 24 hours, andthen soaked in PHB and allowed to equilibrate for at least 12 hours. Theinstruments are regularly cleaned and regularly calibrated using RGPstandards. Upper and lower limits are established by calculating a ±8.8%of the Repository values established by William J. Benjamin, et al., TheOxygen Permeability of Reference Materials, Optom Vis Sci 7 (12s): 95(1997), the disclosure of which is incorporated herein in its entirety:

Material Name Repository Values Lower Limit Upper Limit Fluoroperm 3026.2 24 29 Menicon EX 62.4 56 66 Quantum II 92.9 85 101

Unless otherwise specifically stated or made clear by its usage, allnumbers used in this application should be considered to be modified bythe term “about.”

Films were removed from glass plates and hydrated/extracted in deionizedH₂O for a minimum of 4 hours, transferred to fresh deionized H2O andautoclaved 30 min at 121° C. The cooled films were then analyzed forselected properties of interest in ophthalmic materials as described intable 2. Mechanical tests were conducted in borate buffered salineaccording to ASTM D-1708a, discussed above. The oxygen permeabilities,reported in Dk (or barrer) units, were measured in phosphate bufferedsaline at 35° C., using acceptable films with three differentthicknesses, as discussed above.

The claims, as originally presented and as they may be amended,encompass variations, alternatives, modifications, improvements,equivalents, and substantial equivalents of the embodiments andteachings disclosed herein, including those that are presentlyunforeseen or unappreciated, and that, for example, may arise fromapplicants/patentees and others.

1. A random copolymer of formula (I):

wherein R1 and R5 are the same or different and selected from the groupconsisting of the following radicals:

with the proviso that when R5 is the same and is formula II, R1 is notof formula I, x is 0 to 1000, y is I to 300, L can be the same ordifferent and is selected from the group consisting of urethanes,carbonates, carbamates, carboxyl ureidos, sulfonyls, a straight orbranched C1-C30 alkyl group, a C1-C30 fluoroalkyl group, a C1-C20 estergroup, an alkyl ether, cycloalkyl ether, cycloalkenyl ether, aryl ether,arylalkyl ether, a polyether containing group, an ureido group, an amidegroup, an amine group, a substituted or unsubstituted C1-C30 alkoxygroup, a substituted or unsubstituted C3-C30 cycloalkyl group, asubstituted or unsubstituted C3-C30 cycloalkenyl group, a substituted orunsubstituted C5-C30 aryl group, a substituted or unsubstituted C5-C30arylalkyl group, a substituted or unsubstituted C5-C30 heteroaryl group,a substituted or unsubstituted C3-C30 heterocyclic ring, a substitutedor unsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, a C5-C30 fluoroaryl group,or a hydroxyl substituted alkyl ether and combinations thereof; X⁻ is atleast a single charged counter ion; n is an integer from I to about 300;each R2, R3 and R5 are independently hydrogen, a straight or branchedC1-C30 alkyl group, a C1-C30 fluoroalkyl group, a C1-C20 ester group, analkyl ether, cycloalkyl ether, cycloalkenyl ether, aryl ether, arylalkylether, a polyether containing group, an ureido group, an amide group, anamine group, a substituted or unsubstituted C1-C30 alkoxy group, asubstituted or unsubstituted C3-C30 cycloalkyl group, a substituted orunsubstituted C3-C30 cycloalkenyl group, a substituted or unsubstitutedC5-C30 aryl group, a substituted or unsubstituted C5-C30 arylalkylgroup, a substituted or unsubstituted C5-C30 heteroaryl group, asubstituted or unsubstituted C3-C30 heterocyclic ring, a substituted orunsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, fluorine, a C5-C30fluoroaryl group, or a hydroxyl group; each R4 is independently H or amethyl radical, X is independently a straight or branched C1-C30 alkylgroup, a C1-C30 fluoroalkyl group, a substituted or unsubstituted C5-C30arylalkyl group, an ether, polyether, sulfide, or amino-containing groupand V is independently a polymerizable ethylenically unsaturated organicradical.
 2. The monomer of claim 1 wherein X⁻ is selected from the groupconsisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻, CH₃CO₂ ⁻, HCO₃ ⁻, CH₃SO₄ ⁻,p-toluenesulfonate, HSO4⁻, H₂PO₄ ⁻, NO₃ ⁻, CH₃CH(OH)CO₂ ⁻, SO₄ ²⁻, O₃²⁻, HPO₄ ²⁻ and mixtures thereof.
 3. The monomer of claim 1 wherein X⁻is at least a single charged counter ion and is selected from the groupconsisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻, CH₃CO₂ ⁻, HCO₃ ⁻, CH₃SO₄ ⁻,p-toluenesulfonate, HSO₄ ⁻, H₂PO₄ ⁻, NO₃ ⁻, and CH₃CH(OH)CO₂ ⁻ andmixtures thereof.
 4. The monomer of claim 1 wherein the monomer isselected from the group consisting of monomers having the followingformulae:


5. A monomer mix useful for making polymerized biomaterials comprisingat least one random copolymer of claim 1 and at least second monomer. 6.The monomer mix of claim 5, further compromising in addition to thesecond monomer a hydrophobic monomer and a hydrophilic monomer.
 7. Themonomer mix of claim 5 wherein the second monomer is selected from thegroup consisting of unsaturated carboxylic acids; methacrylic acids,acrylic acids; acrylic substituted alcohols; 2-hydroxyethylmethacrylate,2-hydroxyethylacrylate; vinyl lactams; N-vinyl pyrrolidone (NVP),N-vinyl caprolactone; acrylamides; methacrylamide,N,N-dimethylacrylamide; methacrylates; ethylene glycol dimethacrylate,methyl methacrylate, allyl methacrylate; hydrophilic vinyl carbonates,hydrophilic vinyl carbamate monomers; hydrophilic oxazolone monomers,methacryloxypropyl tris(trimethylsiloxy)silane, ethylene glycoldimethacrylate (EGDMA), allyl methacrylate (AMA) and mixtures thereof.8. A device comprising the random copolymer of claim 1 as a polymerizedcomonomer.
 9. The device of claim 8 wherein the device is a contactlens.
 10. The device of claim 8 wherein the contact lens is a rigid gaspermeable contact lens.
 11. The device of claim 8 wherein the lens is asoft contact lens.
 12. The device of claim 8 wherein the lens is ahydrogel contact lens.
 13. The device of claim 8 wherein the lens is anintraocular lens.
 14. The device of claim 13 wherein the lens is aphakic intraocular lens.
 15. The device of claim 13 wherein the lens isan aphakic intraocular lens.
 16. The device of claim 8 wherein thedevice is a corneal implant.
 17. The device of claim 8 wherein thedevice is selected from the group consisting of heart valves,intraocular lenses, films, surgical devices, vessel substitutes,intrauterine devices, membranes, diaphragms, surgical implants, bloodvessels, artificial ureters, artificial breast tissue, membranes forkidney dialysis machines, membranes for heart/lung machines, catheters,mouth guards, denture liners, ophthalmic devices, and contact lenses.18. A method of making a device comprising: providing a monomer mixturecomprising the random copolymer of claim 1 and at least a secondmonomer; subjecting the monomer mixture to polymerizing and shapingconditions to provide a polymerized device; extracting the polymerizeddevice; and packaging and sterilizing the polymerized device.
 19. Themethod of claim 18 wherein the step of extracting is performed withnon-flammable solvents.
 20. The method of claim 19 wherein theextraction solvent is water.